Comparative Pharmacokinetics and Pharmacodynamics of Synthetic Nicotine

Phase 1

Recruiting

• Conditions: Nicotine Vaping; Nicotine Dependence
• Interventions: Drug: (S)-Nicotine; Drug: (R)- nicotine; Drug: Racemic nicotine

• Registration Number: NCT05962229
• Lead Sponsor: University of California, San Francisco

Brief Summary

In a crossover study, experienced electronic cigarette users will vape 3 different forms of nicotine: natural (derived from tobacco), synthetic, or a 50:50 mixture of both natural and synthetic. The investigators will compare nicotine metabolism, cardiovascular effects, patterns of self-administration, and participants' feelings of craving/withdrawal and enjoyment.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-07-17
• Study First Submitted QC: 2023-07-17
• Study First Posted: 2023-07-27
• Study Start: 2024-12-06
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-02
• Last Update Posted: 2025-04-03
• Primary Completion: 2025-09
• Study Completion: 2025-09

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 18

Inclusion Criteria

• Healthy on the basis of medical history and limited physical examination.
• Current regular user of E-Cigarettes (≥ 15 days in the past 30 days)

Exclusion Criteria

• • Medications

  • Use of medications that are inducers of nicotine metabolizing enzyme CYP2A6 (Example: rifampicin, carbamazepine, phenobarbital, and other anticonvulsant drugs).

  • Use of sympatholytic medications for cardiovascular conditions including hypertension (Example: beta and alpha-blockers).

  • Concurrent use of nicotine-containing medications (Example: nicotine patch, lozenge, gum).

  • Any stimulant medications (example: Adderall) generally given for ADHD treatment.

    • Pregnancy

  • Pregnancy (self-reported and urine pregnancy test)

  • Breastfeeding (determined by self-report)

  • Women of childbearing potential must be using an acceptable method of contraception

    • Inability to read and write in English
    • A known propylene glycol/vegetable glycerin allergy
    • Uncomfortable with getting blood drawn

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
S-nicotine (tobacco) as the starting condition	(R)- nicotine	Participants will spend 8 hours in the hospital research ward where they will vape e-liquid containing 100% (S)-nicotine.
R-nicotine (synthetic) as the starting condition	(R)- nicotine	Participants will spend 8 hours in the hospital research ward where they will vape e-liquid containing 100% (R)-nicotine.
Racemic (50:50 S- and R- nicotine) as the starting condition	(R)- nicotine	Participants will spend 8 hours in the hospital research ward where they will vape e-liquid containing 50% (S)-nicotine and 50% (R)-nicotine.
S-nicotine (tobacco) as the starting condition	Racemic nicotine	Participants will spend 8 hours in the hospital research ward where they will vape e-liquid containing 100% (S)-nicotine.
R-nicotine (synthetic) as the starting condition	Racemic nicotine	Participants will spend 8 hours in the hospital research ward where they will vape e-liquid containing 100% (R)-nicotine.
Racemic (50:50 S- and R- nicotine) as the starting condition	Racemic nicotine	Participants will spend 8 hours in the hospital research ward where they will vape e-liquid containing 50% (S)-nicotine and 50% (R)-nicotine.
S-nicotine (tobacco) as the starting condition	(S)-Nicotine	Participants will spend 8 hours in the hospital research ward where they will vape e-liquid containing 100% (S)-nicotine.
R-nicotine (synthetic) as the starting condition	(S)-Nicotine	Participants will spend 8 hours in the hospital research ward where they will vape e-liquid containing 100% (R)-nicotine.
Racemic (50:50 S- and R- nicotine) as the starting condition	(S)-Nicotine	Participants will spend 8 hours in the hospital research ward where they will vape e-liquid containing 50% (S)-nicotine and 50% (R)-nicotine.

Primary Outcome Measures

Name	Time	Method
Mean Nicotine Exposure Over Time	Up to 7 hours	Plasma nicotine area under the concentrated time curve (AUC) (ng/ml\*h)

Secondary Outcome Measures

Name	Time	Method
Mean Amount of Nicotine Consumed Over Time	120 minutes	Nicotine self-administration determined by device weight change before and after use multiplied by the nicotine concentration in the e-liquid

Trial Locations

Locations (1)

Zuckerberg San Francisco General Hospital (ZSFG); 🇺🇸 San Francisco, California, United States